Multiparametric detection in a fluidic microsystem

Abstract

Disclosed is a method for measuring properties of particles that move through a fluidic microsystem, the particles being suspended in a liquid. According to the inventive method, a first parameter of a specific particle is first measured at a first test station ( 11 ). A second parameter of the particle is then measured at an interval from the first measurement at a second test station ( 12 ) which is spatially separated from the first test station ( 11 ), and the first and second parameters are jointly evaluated in a correlated manner, the first and second parameters being characteristic of different properties of the tested particle. The evaluation comprises a comparison of the first and second parameters with predetermined expected values. Another measurement is taken or manipulations are performed on the tested particle according to the result of the comparison. Also disclosed is a fluidic microsystem that is designed for implementing the inventive method.

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       29 . A method for measuring properties of particles, which move through a fluidic microsystem suspended in a liquid, comprising: 
 a) a first measurement of a first parameter of a specific particle at a first measuring station,    b) a second measurement of a second parameter of the particle at an interval in time from the first measurement at a second measuring station, which is spatially separated from the first measuring station, and    c) a joint, correlated evaluation of the first and second parameters,    d) the first and second parameters being characteristic for different properties of the measured particle,    e) the evaluation comprising a comparison and/or a correlation of the first and second parameters with predefined expected values, and    f) a further measurement or manipulation follows on the measured particle as a function of the result of the comparison.    
   
   
       30 . The method according to  claim 29 , wherein a morphologic parameter of the particle is determined as the first or second parameter.  
   
   
       31 . The method according to  claim 30 , wherein the measurement comprises a transmitted light measurement and/or an impedance measurement and/or an electrical measurement and/or a magnetic measurement.  
   
   
       32 . The method according to claims  29 , wherein a material parameter of the particle, which is characteristic for the chemical or biological composition of the particle, is determined as the first or second parameter.  
   
   
       33 . The method according to  claim 32 , wherein the measurement comprises a fluorescence measurement.  
   
   
       34 . The method according to  claim 30 , wherein the morphological parameter is measured chronologically before the material parameter.  
   
   
       35 . The method according to  claim 32 , wherein the material parameter is measured chronologically before the morphological parameter.  
   
   
       36 . The method according to  claim 29 , wherein solid particles or liquid particles delimited from the suspension medium pass the measuring stations as the synthetic or biological particles.  
   
   
       37 . The method according to  claim 36 , wherein the biological particles comprise biological cells, cell groups, cell components or biologically relevant macromolecules or compositions thereof.  
   
   
       38 . The method according to  claim 29 , wherein the measured particle moves past the measuring stations with the liquid during the first and second measurements.  
   
   
       39 . The method according to  claim 29 , wherein the at least one further measurement performed as a result of the comparison comprises a measurement on the resting particle, which is fixed in the liquid.  
   
   
       40 . The method according to  claim 29 , wherein at least one manipulation element and/or at least one further measuring station in the microsystem is actuated as a function of the result of the comparison of at least two measurements.  
   
   
       41 . The method according to  claim 40 , wherein at least one dielectric cage, at least one dielectric switch, at least one dielectric manipulator and/or at least one optical manipulator and/or one magnetic manipulator are actuated as a function of the result of the comparison.  
   
   
       42 . The method according to  claim 29 , wherein the time, the direction, and/or the velocity of the passage of the measured particle past the measuring stations is analyzed from the measured parameters.  
   
   
       43 . The method according to  claim 29 , wherein multiple particles are measured sequentially and evaluated individually.  
   
   
       44 . The method according to  claim 29 , wherein a time dependence of at least one of the measured parameters is recorded at multiple measuring stations.  
   
   
       45 . The method according to  claim 29 , wherein the particles are transferred from a first channel into a second channel, in which there is a different chemical environment than in the first channel and in which the first and following measurements are performed directly after the transfer from the first channel.  
   
   
       46 . A measuring device for measuring properties of particles, which move through a fluidic microsystem suspended in a liquid, having: 
 a) a first measuring station for a first measurement of a first parameter of a particle,    b) a second measuring station for a second measurement of a second parameter of the particle, which is positioned spatially separated from the first measuring station, and    c) an evaluation device for joint, correlated evaluation of the first and second parameters,    d) the first and second measuring stations being set up for measuring parameters which are characteristic for different properties of the particle,    e) while the analysis device contains a comparator device for comparing the first and second parameters to predefined expected values, and    f) using the comparator device, a signal may be generated for further measurements or manipulations on the particle as a function of the result of the comparison.    
   
   
       47 . The measuring device according to  claim 46 , wherein the first measuring station comprises a transmitted light detector device or an impedance detector.  
   
   
       48 . The measuring device according to  claim 46 , wherein the second measuring station comprises a fluorescence detector device and/or an electrical detector device and/or a magnetic detector device.  
   
   
       49 . The measuring device according to  claim 48 , wherein the fluorescence detector device is shielded to reduce interfering scattered light using a scattered light mask.  
   
   
       50 . A fluidic microsystem which is equipped with a measuring device according to  claim 46 .  
   
   
       51 . The fluidic microsystem according to  claim 50 , wherein the first and second measuring stations are positioned in a joint channel of the fluidic microsystem.  
   
   
       52 . The fluidic microsystem according to  claim 50 , wherein focusing electrodes are provided upstream, before the arrangement of the measuring stations.  
   
   
       53 . The fluidic microsystem according to  claim 50 , which comprises two channels, which are connected via a passage opening in a partition wall, wherein the passage opening is provided upstream, before the arrangement of the measuring stations, and is equipped with a manipulation element for transferring particles from the first into the second channel.  
   
   
       54 . The fluidic microsystem according to  claim 50 , wherein further measuring stations and/or manipulation elements are provided downstream, after the arrangement of the measuring stations.  
   
   
       55 . The fluidic microsystem according to  claim 54 , wherein the comparator device is connected to the measuring stations and/or manipulation elements, so that these may be actuated using the signal of the comparator device.  
   
   
       56 . The fluidic microsystem according to  claim 55 , wherein the measuring stations and/or manipulation elements comprise at least one dielectric cage, at least one dielectric switch, at least one dielectric manipulator, and/or at least one optical manipulator.